This project represents continuing research into the relationship between psychotogenic procedures and brain amines. Specifically, we are investigating the psychopharmacology of indoleamine (especially LSD) and phenylethylamine hallucinogens and their effects on metabolism ("binding," synthesis, storage, uptake, release, enzyme activity, compartmentation and catabolism) of the brain amines (5-hydroxytryptamine, norepinephrine, dopamine). The experiments proposed are designed to ultimately elucidate the mechanisms accountable for amine-dependent and amine-mediated behavioral effects of psychotomimetics, for the differences among the indoleamine hallucinogens and between the indoleamines and phenylethylamines, and for tolerance with time-course measures of drug and amine metabolism and disposition. In addition, these studies are aimed at exploring basic mechanisms of central monoaminergic transmission such as binding and uptake of amines, compartmentation, amine and drug receptors, storage pools and enzymes that govern such processes. Neuroendocrinological studies provide a new dimension in the search for peripheral measures to deduce central monoaminergic and receptor activity. The effects of various hypothalamic, midbrain and brainstem lesions on brain amines and drug-induced behavioral effects help to further specify the CNS sites responsible for drug response. Thus, we have outlined a sequence of studies to determine further the role of amines, drugs and neuronal activity in the chain of critical neurochemical events to behavioral changes. Investigation of the regional, cellular and subcellular localization in the brain of hallucinogenic drugs, of the amines, and of the drug-induced shifts in subcellular compartments is being facilitated by the utilization of radioactive tracers, by the application of refined separation techniques (density gradient centrifugation, ion-exchange, thin-layer, affinity and gas chromatography), by lesion techniques and by radioimmune assays.